Estrogens are well known to produce dramatic increases in uterine blood flow. This estrogen-induced response is produced by activation of some mediator(s) rather than a direct effect of the hormone on the vessel wall. Agents such as adenosine, the adenine nucleotides, and the prostaglandins are known to be potent uterine vasodilators, and have been proposed to mediate the estrogen-stimulated response. Recent evidence strongly suggests that prostacyclin, a product of endoperoxide metabolism synthesized in vascular endothelium, is the local regulator of vasodepressor responses in numerous organs and in various species. The fact that prostaglandin synthesis and estrogen-induced uterine blood flow are both inhibited by corticosteroids makes attractive a hypothesis which links prostacyclin synthesis to the estrogen-blood flow response. Utilizing a well-established sheep model, specifically designed for continuous blood flow measurements in the chronic state, we propose to explore the role of the prostaglandins and adenosine in the regulation of uterine blood flow by (1) observing the blood flow responses to intra-arterial infusions of prostacyclin and arachidonic acid, (2) attempting to suppress estrogen and arachidonic acid induced flow increases with inhibitors of prostaglandin synthesis, and (3) elucidating the relationship between adenosine and prostaglandin synthesis. The proposed study should provide basic information relating to the regulation of uterine blood flow and ultimately improve our understanding of perinatal well-being.